Respiratory Syncytial Virus (RSV) is the leading viral cause of death in children less than 5 years old and pediatric lower respiratory tract infection and infant hospitalization. Elderly and immune compromised adults are also high risk population. Currently, there is no approved vaccine on the market. Inhibitors of RSV are useful to limit the establishment and progression of infection by RSV as well as in diagnostic assays for RSV.
(3-Amino-oxetan-3-ylmethyl)-[2-(5,5-dioxo-5,6,7,9-tetrahydro-5lambda*6*-thia-8-aza-benzocyclohepten-8-yl)-6-methyl-quinazolin-4-yl]-amine (compound (I)) was disclosed in WO2013020993 as an effective respiratory syncytial virus (RSV) inhibitor. The compound (I) is also named as N-[(3-Aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-amine.
Form D of compound (I) was found as metastable form at the early research stage and the hygroscopicity of Form D of compound (I) makes it not suitable for further drug development. As an action of risk mitigation, comprehensive studies were conducted. As one of the objections of this patent, several novel crystalline forms were synthesized and characterized, showing significantly improved hygroscopicity compared with Form D of compound (I). Meanwhile, developing novel crystalline forms of compound (I) with good stability and/or aqueous solubility are also one of the objectives of this patent respectively. These novel crystalline forms enhanced the developability of compound (I) fundamentally.
The present disclosure relates generally to novel crystalline forms of compound (I), and processes to make those forms.